Anabolic effects and inhibition of interleukin 6 production induced by neridronate on human osteoblasts

• Main Authors: S. Niccolini, F. Chellini, F. Baldi, P. Ferrata, D. Gambera, C. Capperucci, B. Frediani, A. Spreafico, L. Bocchi, R. Marcolongo
• Format: Article
• Language: English
• Published: PAGEPress Publications 2011-09-01
• Series: Reumatismo
• Online Access: http://www.reumatismo.org/index.php/reuma/article/view/283
• ISSN: 0048-7449; 2240-2683

Bisphosphonates (BPs) are pharmacological compounds widely used in the treatment of a variety of bone-related diseases, particularly where the bone-turnover is skewed in favour of osteolysis. The mechanisms by which BPs reduce bone-resorption directly acting on osteoclasts (OCs) are now largely clarified even at molecular level. The researches concerning the BPs effects on osteoblasts (OBs) have instead shown variable results. Objectives: We have investigated the efficacy of neridronate (NER), an amino-BP, as anabolic agent on human OBs. Moreover, we have tried to verify if NER is able to negatively modulate the production of IL-6 on OBs stimulated or not by the pro-inflammatory cytokine Il-1b. Methods: We have tested if different concentrations of NER (from 10-11M to 10-3M), added to primary human OB cultures, could affect the cells number, the endogenous cellular alkaline phosphatase (ALP) activity, the collagen I (COLI) synthesis, the formation of mineralized nodules and the IL-6 production. Our experimental approach was performed testing a wide range of NER concentrations because, under physiological conditions, OBs seems to be exposed to variable and transient levels of the drug. Results: Our results show that NER doesn’t negatively affect in vitro the viability, proliferation and cellular activity of human OBs, even after 20 days of exposure to concentrations ²10-5 M (therapeutic dose). In addition, NER seems to enhance the differentiation of cultured OBs in mature bone-forming cells. A maximum increase of COL-I synthesis (+25% after 4 days; p<0.05), ALP activity (+50% after 10 days; p<0.01) and mineralized nodules (+48% after 20 days; p<0.05) was observed in cultures treated with NER 10-8M. A maximal reduction of IL-6 secretion (-24% on IL-1b stimulated cultures and -29% on unstimulated cultures) was observed for NER 10-9 M. Conclusions: These results encourage the use of neridronate in therapy of demineralizing metabolic bone disorders.